SOP TITLE:
Site Initiation, Activation, Conduct and Close-out
SOP Version
No:
Date:
01
SOP No:
Version: 1
Effective Date:
Standard Operating Procedure
Title: Site Initiation, Activation, Conduct and Close-out
SIGNATURE
DATE
NAME
PREPARED BY
REVIEWED BY
QA UNIT
AUTHORITY
APPROVAL
AUTHORITY
This template has been freely provided by Dr Sreedhar Tirunagari via The
Global Health Network. Please reference The Global Health Network when
you use it, and share your own materials in exchange.
www.theglobalhealthnetwork.org.
Page 1 of 10
SOP TITLE:
Site Initiation, Activation, Conduct and Close-out
SOP Version
No:
Date:
01
7.1 Purpose
To describe the process which ensures that the site is organized and prepared for the proper
conduct of the research study at [INSTITUTION]. This standard operating procedure (SOP) also
describes the processes to be followed at site initiation, activation, conduct and closeout of research
study at [INSTITUTION].
7.2 Scope
This SOP will apply to all pharma sponsored research study initiation, activation, conduct and closeout at [INSTITUTION].
7.3 Procedure
A research study should be initiated at a site only after investigator and Sponsor/CRO involved in the
study is satisfied that essential documents, agreements and approvals are all in place. The site
initiation process is designed to ensure that;



The site has all essential documents in place for the site to conduct the study in compliance
with the approved protocol and applicable regulatory guidelines.
The site is aware of all the sponsor’s procedures and SOPs for study conduct (such as safety
recording and reporting, amendments, notification of any urgent safety measures/ violations
or serious breaches) and has read and understood each.
The site is met with all the required regulatory and sponsor requirements.
7.3.1 Preparing site for Site Initiation Visit
a. For preparing the site for initiation the investigator(s) or Clinical Trial Coordinator (CTC) should:




Confirm the available date and time with the clinical research team that must attend the
meeting and arrange the most suitable meeting date, time and place.
Request an agenda for the visit from the sponsor; circulate the same to each team member.
Confirm that investigator and team has reviewed the Protocol and Investigator’s Brochure
(IB) and any up-to-date information on investigational product (IP). The Investigator(s) must
prepare a list of questions if any to be asked in the SIV.
Ensure that the procedures stated in the study protocol are applicable at the site and fully
understood.
This template has been freely provided by Dr Sreedhar Tirunagari via The
Global Health Network. Please reference The Global Health Network when
you use it, and share your own materials in exchange.
www.theglobalhealthnetwork.org.
Page 2 of 10
SOP TITLE:
Site Initiation, Activation, Conduct and Close-out
SOP Version
No:
Date:
01




Confirm that all documents required by Institutional Ethics Committee (IEC) are available.
Confirm that the clinical trial agreement (CTA), indemnification letter and budget are
finalized and signed.
Notify appropriate departments regarding the sponsor/CRO visit (e.g., Laboratories,
pharmacy, CT scan, bone scan and x-ray, etc).
File all essential documents in TMF (or sponsor-supplied Investigator Study File), and
compile any outstanding documents to provide to the Clinical Research Associate (CRA) at
the initiation meeting.
7.3.2 During the Site Initiation Visit
a. During the initiation visit the investigator(s) or Clinical Trial Coordinator (CTC) should:

















Ensure that the Investigator’s Trial Master File (TMF) contains the following mentioned
applicable items and all the required regulatory documents:
Signed protocol and Investigator Statement o Signed and executed Investigator contract CVs
and licenses of key site study staff
Financial Disclosure forms
Investigator Undertaking (IU)
Form FDA 1572 for IND studies
IEC approval letter for the protocol o IEC membership roster (updated)
IEC approved informed consent form
Institutional and/or other regulatory authority approvals or Valid clinical/other laboratory
licensure
Laboratory normal value ranges
Notice that indicates the study has been submitted to the regulatory authorities (if
applicable).
Investigator Brochure, if applicable
Case Report Forms (CRF)
Investigational product inventory management forms or any other essential documents.
Provide the study members name involved in the study and their responsibilities in the duty
delegation to the monitor/CRA.
Provide original and updated curriculum vitae of all study personnel / Investigators involved,
as per sponsor requirements (if not provided earlier).
Ensure that the names and contact numbers of the relevant medical and study personnel of
the sponsor are available and documented clearly.
Ensure that all relevant study site personnel fill out the Site Personnel/Signature Log and
Training Log.
This template has been freely provided by Dr Sreedhar Tirunagari via The
Global Health Network. Please reference The Global Health Network when
you use it, and share your own materials in exchange.
www.theglobalhealthnetwork.org.
Page 3 of 10
SOP TITLE:
Site Initiation, Activation, Conduct and Close-out
SOP Version
No:
Date:
01








Check that the procedures and plans for storage, dispensing and return of IP have been
agreed and finalized with the Sponsor and Pharmacist (if applicable).
In case of paper CRF’s: Check that the quantity of CRFs that have been requested or shipped
to the study site are sufficient for the number of Participants/patients that are likely to be
recruited into the study also allowing for the archiving of one set of intact, unused CRFs
Check that other related supplies are available or are to be shipped to the study site at a
later date, and that they are available in sufficient quantities.
Check that laboratory facilities and arrangements for the dispatch of samples to the central
laboratory are organized and that any specialized equipment that may be required will be
available throughout the period of the trial, e.g. collection kits, centrifuge machine, freezer,
etc.
Ensure that monitor/CRA gives sufficient time to CTC for CRF completion training.
Ensure and understand the requirements of the sponsors/CRO regarding source documents
and raw data, which will be required during monitoring visits to enable the monitor/CRA to
perform source data verification at each monitoring visit.
Ensure that the procedures relating to the archiving of study records at the end of the study
is agreeable to the sponsor.
During the initiation visit the Investigator or delegate (for investigator initiated study) and
monitor/CRA (for sponsor study) will provide a protocol-specific training session to all the
members of the research team who will be involved in the research study. The investigator
or monitor/CRA will ensure that the attendance sheets and other training documentation
are completed.
b. The protocol-specific training session will include, but is not limited to, the following:











Aim and Objective of the protocol
Time and events schedule for the protocol
Subject recruitment
Obtaining informed consent
Procedure for dispensing the IP
IP storage and records
Protocol-specific forms and procedures
Source documentation
Adverse event reporting
Additional information from the Investigator’s Meeting (IM)
Any other relevant information
This template has been freely provided by Dr Sreedhar Tirunagari via The
Global Health Network. Please reference The Global Health Network when
you use it, and share your own materials in exchange.
www.theglobalhealthnetwork.org.
Page 4 of 10
SOP TITLE:
Site Initiation, Activation, Conduct and Close-out
SOP Version
No:
Date:
01
c. The Investigator, monitor/CRA and CTC will:


Develop a recruitment plan for subjects
Identify a back-up to the primary CTC
7.3.3 Study Activation and Initiation Visit Follow-Up
In preparation for study activation:






Confirm that the sponsor sends a written summary of key discussions and agreements made
during the site initiation visit. Follow-up if necessary.
Confirm readiness of the site to start the study.
Confirm the receipt of all study-related materials such as CRFs, laboratory supplies,
investigational product(s).
Distribute protocol summaries and worksheets, if not done previously (the sponsor may
provide study-related worksheets, however the site can prepare one).
Notify all appropriate departments that the study is ready to enroll participants.
Initiate study recruitment strategies and begin enrolling study patients/participants.
7.3.4 Study conduct
a. Once the site is activated and starts recruiting patients, the Investigator and CTC will ensure the
following:







All study activities are accomplished according to the protocol and applicable regulatory
regulations.
Subjects sign the correct version of the consent form before any study-related procedures
are accomplished.
Data collected in the Case Report Form (CRF) are supported by source documents.
Protocol deviations/non compliance/violations/waivers if any should be notified to the IEC
(Refer SOP for IEC communication) and the same must be documented in the source
documents and appropriate CRF.
Adverse events are reflected in the source documents and captured in the CRF. (With
appropriate term, grade, causality, start and stop date and CCM given if any.)
Serious Adverse events (SAEs) are reported to the Sponsor/CRO and IEC within specified
time frame (refer SOP for SAE reporting).
SUSAR and CIOMS should be notified in the timely manner to the IEC.
This template has been freely provided by Dr Sreedhar Tirunagari via The
Global Health Network. Please reference The Global Health Network when
you use it, and share your own materials in exchange.
www.theglobalhealthnetwork.org.
Page 5 of 10
SOP TITLE:
Site Initiation, Activation, Conduct and Close-out
SOP Version
No:
Date:
01

The IP is being dispensed correctly and IP accountability records are being maintained.
b. While the study is ongoing, the CTC will ensure the following




The Sponsor/CRO is informed of all significant study events and staff members are
documenting critical interactions with the Sponsor/CRO.
Biological samples are being obtained, handled, stored, and shipped appropriately.
Study supplies remain adequate. Study records remain confidential.
All equipment is calibrated regularly and maintenance records are being kept.
7.3.5 Premature Termination or Suspension of a Study
a. If the research study is prematurely terminated or suspended for any reason, the
investigator/institution should:




Immediately inform the IEC regarding the premature termination of the study in the format
specified in the IEC SOP.
Promptly inform the trial participants and include, where appropriate, the reason for
suspension / early termination of the study.
Assure appropriate therapy and follow-up for the participants, and, where required by the
applicable regulatory requirement(s), should inform the regulatory authority (ies).
The PI should maintain documents as specified in the TMF list and take measures to prevent
accidental or premature destruction
In addition:
b. If the PI terminates or suspends a research study without prior agreement of the sponsor, the PI
should:

Promptly inform the sponsor and the IEC regarding the termination Provide the sponsor and
the IEC with a detailed written explanation of the termination or suspension.
c. If the sponsor terminates or suspends a research study, the PI should:

In case the sponsor chooses to or is required to terminate prematurely or suspend the
research study, then the sponsor should notify the investigator(s), institution(s), the ethics
committee and the regulatory authorities accordingly. The notification should document the
This template has been freely provided by Dr Sreedhar Tirunagari via The
Global Health Network. Please reference The Global Health Network when
you use it, and share your own materials in exchange.
www.theglobalhealthnetwork.org.
Page 6 of 10
SOP TITLE:
Site Initiation, Activation, Conduct and Close-out
SOP Version
No:
Date:
01
reason(s) for the termination or suspension by the sponsor or by the investigator /
institution
7.3.6 Site close-out
a. Preparing the site for study close-out visits:







After the last patient has completed all scheduled visits associated with the study, arrange a
mutually convenient date and time with the monitor/CRA to conduct the study close-out
visit.
Request the monitor/CRA for the visit agenda so key research personnel such as PI, Co I,
CTC, research nurse and other team members will be available, as appropriate.
Ensure all regulatory documentation and case report forms (CRFs) not previously monitored
are complete and available for review.
Ensure all data queries received to date have been resolved.
Inventory IPs supply and complete final accountability records. If previously instructed to
return or destroy IP, assure all required documentation is filed in the appropriate TMF for
monitor/CRA review.
Arrange monitor/CRA meeting with the PI and/or Co I and CTC to discuss any outstanding
issues.
PI will ensure that all outstanding payments are cleared as per CTA.
b. Managing the study close-out visit:





Ensure all documentation (e.g., regulatory correspondence) is filed appropriately and ready
for the monitor/CRA to review during the close-out visit.
Discuss all open study-related issues and what steps will be taken to resolve them in order to
satisfy the sponsor/CRO requirement(s).
Review with the monitor/CRA the list of outstanding issues related to regulatory documents,
source data verification, IP reconciliation, and any requirements for data retention and
storage.
Discuss any concerns regarding the possibility of a quality assurance audit and/or inspection
by IEC or external regulatory bodies. Include the CTC as appropriate.
If the study involved electronic data capture, determine when hard copies/CD of all CRFs will
be provided to [Institution], if applicable.
This template has been freely provided by Dr Sreedhar Tirunagari via The
Global Health Network. Please reference The Global Health Network when
you use it, and share your own materials in exchange.
www.theglobalhealthnetwork.org.
Page 7 of 10
SOP TITLE:
Site Initiation, Activation, Conduct and Close-out
SOP Version
No:
Date:
01


The PI is responsible for ensuring the appropriate follow-up, per the protocol, for any
participant experiencing an ongoing unanticipated problem (e.g., serious adverse event) at
study end and providing this information to the sponsor/CRO, assuring all requirements
have been met.
Arrange meeting of the PI and monitor/CRA to discuss any future considerations (e.g.,
publication of study data or future studies).
c. Follow-up after the study close-out visit










For any remaining IP(s), ensure the item(s) is returned to the sponsor/CRO per their
requirements.
If the randomization code for any IP was broken for any reason, ensure complete
documentation has been filed.
Ensure return or destruction of all other study-related materials, such as unused lab kits and
CRFs.
Ensure any equipment on loan from the sponsor is returned or if mutually agreed by both
the parties can be retained at the site.
After all data queries have been resolved, check TMF, subject files and other study files for
completeness.
Arrange for transfer of study documents to secure storage.
Submit the Final Closure Report to the IEC, in accordance with IEC SOP for Study Completion
or Closure.
Provide the sponsor/CRO with a copy of the IEC closure letter.
Verify participant reimbursement or compensation if any have been distributed per the
study budget, as outlined in the Informed Consent and CTA.
If the informed consent and CTA, protocol or contract state subjects will be informed of their
treatment arm, ascertain from the sponsor how and when this will be completed.
7.4 Applicable Staff
This SOP applies to all the personals of the clinical research team and others who may be responsible
for site initiation, activation, conduct and close-out at [INSTITUTION].
These include the following:
This template has been freely provided by Dr Sreedhar Tirunagari via The
Global Health Network. Please reference The Global Health Network when
you use it, and share your own materials in exchange.
www.theglobalhealthnetwork.org.
Page 8 of 10
SOP TITLE:
Site Initiation, Activation, Conduct and Close-out
SOP Version
No:
Date:
01





Investigator
Research Team
CTC
Research Nurse
Support staff
7.5 Staff responsible for Implementation
The PI and the research team will ensure that the research team involved in the conduct of the study
will comply with this site SOP and research members involved in the study are following this SOP
while communicating with sponsor/CRO.
The PI will ensure that at the time of implementation of the SOP, that the research team at the
DEPARTMENT OF CLINICAL RESEARCH in [Institution] are trained and in the event that an SOP is
modified, provide training regarding the change(s) and ensure their compliance with the changes.
Inform IEC that this site SOP will be implemented within the institution.
References
21 CFR 312.50 General responsibilities of sponsors
21 CFR 312.56 Review of ongoing investigations
21 CFR 312.59 Disposition of unused supply of investigational drug
21 CFR 312.60 General responsibilities of investigators
21 CFR 312.62 Investigator recordkeeping and record retention
21 CFR 312.64 Investigator reports
21 CFR 312.66 Assurance of IRB review
21 CFR 312.68 Inspection of investigator's records and reports
21 CFR 54.6 – Record Keeping and Record Retention
CDSCO guidelines: Appendix V
Good Clinical Practices
This template has been freely provided by Dr Sreedhar Tirunagari via The
Global Health Network. Please reference The Global Health Network when
you use it, and share your own materials in exchange.
www.theglobalhealthnetwork.org.
Page 9 of 10
SOP TITLE:
Site Initiation, Activation, Conduct and Close-out
SOP Version
No:
Date:
01
ICH Guidelines for Good Clinical Practice (E6)
May 1997 International Conference on Harmonization (ICH)
Schedule Y
This template has been freely provided by Dr Sreedhar Tirunagari via The
Global Health Network. Please reference The Global Health Network when
you use it, and share your own materials in exchange.
www.theglobalhealthnetwork.org.
Page 10 of 10